Ste Marie Linda, Palmiter Richard D
Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Endocrinology. 2003 Oct;144(10):4427-32. doi: 10.1210/en.2003-0561. Epub 2003 Jun 26.
Norepinephrine (NE) and epinephrine (Epi) help maintain normal blood glucose levels by stimulating glucagon release, glycogenolysis, and food consumption, and by inhibiting insulin release. The absence of NE and Epi in dopamine beta-hydroxylase-null (Dbh-/-) mice results in chronically low blood glucose levels, an impaired glucagon response to hypoglycemia, and elevated insulin levels. Nevertheless, Dbh-/- mice have normal glycogen levels and degrade it normally during a fast. Dbh-/- mice defend blood glucose levels better than controls in an insulin tolerance test but have increased sensitivity to glucose-stimulated insulin secretion and respond normally in a glucose tolerance test. Pharmacological evidence indicates that the hyperinsulinemia results from lack of alpha2-adrenoreceptor stimulation and increased parasympathetic tone. Dbh-/- mice eat normally after challenges with modest levels of insulin or 2-deoxyglucose but fail to eat under more extreme conditions when control mice still do. We suggest that the primary difference in Dbh-/- mice is chronic hyperinsulinemia associated with an altered glucose set point. However, these animals compensate for NE/Epi-mediated glycogenolysis and feeding.
去甲肾上腺素（NE）和肾上腺素（Epi）通过刺激胰高血糖素释放、糖原分解和食物摄取，并抑制胰岛素释放，来帮助维持正常的血糖水平。多巴胺β-羟化酶缺失（Dbh-/-）小鼠体内缺乏NE和Epi，导致血糖水平长期偏低、胰高血糖素对低血糖的反应受损以及胰岛素水平升高。然而，Dbh-/-小鼠的糖原水平正常，且在禁食期间能正常降解糖原。在胰岛素耐量试验中，Dbh-/-小鼠比对照组更能维持血糖水平，但对葡萄糖刺激的胰岛素分泌敏感性增加，在葡萄糖耐量试验中反应正常。药理学证据表明，高胰岛素血症是由于缺乏α2-肾上腺素能受体刺激和副交感神经张力增加所致。用适度水平的胰岛素或2-脱氧葡萄糖刺激后，Dbh-/-小鼠进食正常，但在更极端的条件下，当对照小鼠仍能进食时，它们却无法进食。我们认为，Dbh-/-小鼠的主要差异在于与葡萄糖设定点改变相关的慢性高胰岛素血症。然而，这些动物能代偿NE/Epi介导的糖原分解和进食。
